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Potential predictive factors for microvascular invasion in hepatocellular carcinoma classified within the Milan criteria

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Abstract

Background

Microvascular invasion (mvi) is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. However, mvi is difficult to detect preoperatively. The aim of this study was to clarify the risk factors of postoperative recurrence and investigate predictive factors of mvi before hepatectomy for HCC classified within the Milan criteria.

Methods

One hundred fifty-nine patients with hepatocellular carcinoma (HCC) classified within the Milan criteria, who underwent hepatectomy, were enrolled in this study. We investigated the risk factors of recurrence. In addition, we divided them into two groups: mvi-negative group and mvi-positive group, based on pathological findings after surgery. We compared the clinicopathological factors between the two groups and determined the risk factors for mvi.

Results

Overall survival rate at 1, 3, and 5 years were 91.6%, 80.5%, and 74.9%, and the recurrence-free survival rate at 1, 3, and 5-years were 72.3%, 51.6%, and 37.2%. Risk factor analysis for tumor recurrence revealed that total bilirubin, albumin, ICGR15, AFP-L3, tumor number, mvi, and tumor stage had a significant predictive value. Multivariate analysis revealed that tumor number and mvi were significant independent risk factors for tumor recurrence. Predictive analysis for risk factors of mvi revealed that multiple tumors and AFP-L3 > 10% were significant independent risk factors for mvi in HCC classified within the Milan criteria.

Conclusions

The mvi was one of the independent risk factors for tumor recurrence in HCC classified within the Milan criteria. Multiple tumors and high AFP-L3 value were independent predictive factors for mvi.

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Abbreviations

ICGR15:

Retention rate of indocyanine green 15 min after administration

AFP-L3:

Lens culinaris agglutinin A-reactive fraction of α-fetoprotein

References

  1. Omata M, Lesmana LA, Tateishi R et al (2010) Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 4:439–474

    Article  PubMed  PubMed Central  Google Scholar 

  2. Takayama T, Makuuchi M, Hirohashi S et al (1998) Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology 28:1241–1246

    Article  CAS  PubMed  Google Scholar 

  3. Zhang BH, Yang BH, Tang ZY (2004) Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 130:417–422

    PubMed  Google Scholar 

  4. Nagasue N, Uchida M, Makino Y et al (1993) Incidence and factors associated with intrahepatic recurrence following resection of hepatocellular carcinoma. Gastroenterology 105:488–494

    Article  CAS  PubMed  Google Scholar 

  5. Yang Y, Nagano H, Ota H et al (2007) Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection. Surgery (St. Louis) 141:196–202

    Article  Google Scholar 

  6. Figueras J, Jaurrieta E, Valls C et al (2000) Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy. J Am Coll Surg 190:580–587

    Article  CAS  PubMed  Google Scholar 

  7. Michel J, Suc B, Montpeyroux F et al (1997) Liver resection or transplantation for hepatocellular carcinoma? Retrospective analysis of 215 patients with cirrhosis. J Hepatol 26:1274–1280

    Article  CAS  PubMed  Google Scholar 

  8. Sarasin FP, Giostra E, Mentha G et al (1998) Partial hepatectomy or orthotopic liver transplantation for the treatment of resectable hepatocellular carcinoma? A cost-effectiveness perspective. Hepatology 28:436–442

    Article  CAS  PubMed  Google Scholar 

  9. Mazzaferro V, Regalia E, Doci R et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693–699

    Article  CAS  PubMed  Google Scholar 

  10. Befeler AS, Di Bisceglie AM (2002) Hepatocellular carcinoma: diagnostics and treatment. Gastroenterology 122:1609–1619

    Article  PubMed  Google Scholar 

  11. Bismuth H, Majno PE, Adam R (1999) Liver transplantation for hepatocellular carcinoma. Semin Liver Dis 19:311–322

    Article  CAS  PubMed  Google Scholar 

  12. Iwatsuki S, Starzl TE, Sheahan DG (1991) Hepatic resection versus transplantation for hepatocellular carcinoma. Ann Surg 214:221–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bismuth H, Chiche L, Adam R et al (1992) Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg 218:145–151

    Article  Google Scholar 

  14. Roayaie S, Frischer JS, Emre SH et al (2002) Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg 235:533–539

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tovuu LO, Imura S, Utsunomiya T et al (2013) Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma. Int J Clin Oncol 18:651–656

    Article  CAS  PubMed  Google Scholar 

  16. Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236

    Article  PubMed  Google Scholar 

  17. Huppertz A, Haraida S, Kraus A et al (2005) Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT-initial observations. Radiology 234:468–478

    Article  PubMed  Google Scholar 

  18. Bolondi L, Gaiani S, Celli N et al (2005) Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma. Hepatology 42:27–34

    Article  PubMed  Google Scholar 

  19. Liver Cancer Study Group of Japan Primary Liver Cancer in Japan (1990) Clinicopathologic features and results of surgical treatment. Ann Surg 211:277–287

    Google Scholar 

  20. Izumi R, Shimizu K, Ii T et al (1994) Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection. Gastroenterology 106:720–727

    Article  CAS  PubMed  Google Scholar 

  21. Otto G, Heuschen U, Hofmann WJ et al (1998) Survival and recurrence after liver transplantation versus liver resection for hepatocellular carcinoma: a retrospective analysis. Ann Surg 227:424–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jonas S, Bechstein WO, Steinmüller T et al (2001) Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology 33:1080–1086

    Article  CAS  PubMed  Google Scholar 

  23. Eguchi S, Takatsuki M, Hidaka M et al (2010) Predictor for histological microvascular invasion of hepatocellular carcinoma: a lesson from 229 consecutive cases of curative liver resection. World J Surg 34:1034–1038

    Article  PubMed  Google Scholar 

  24. Koike Y, Shiratori Y, Sato S et al (2001) Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer (Phila) 91:561–569

    Article  CAS  Google Scholar 

  25. Fujiki M, Takada Y, Ogura Y et al (2009) Significance of des-gamma-carboxy prothrombin in selection criteria for living donor liver transplantation for hepatocellular carcinoma. Am J Transplant 9:2362–2371

    Article  CAS  PubMed  Google Scholar 

  26. Shirabe K, Itoh S, Yoshizumi T et al (2007) The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol 95:235–240

    Article  CAS  PubMed  Google Scholar 

  27. Shirabe K, Aishima S, Taketomi A et al (2011) Prognostic importance of the gross classification of hepatocellular carcinoma in living donor-related liver transplantation. Br J Surg 98:261–267

    Article  CAS  PubMed  Google Scholar 

  28. Sterling RK, Wright EC, Morgan TR et al (2012) Frequency of elevated hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C. Am J Gastroenterol 107:64–74

    Article  CAS  PubMed  Google Scholar 

  29. Saito Y, Shimada M, Utsunomiya T et al (2012) Prediction of recurrence of hepatocellular carcinoma after curative hepatectomy using preoperative Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein. Hepatol Res 42:887–894

    Article  PubMed  Google Scholar 

  30. Esnaola NF, Lauwers GY, Mirza NQ et al (2002) Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation. J Gastrointest Surg 6:224–232

    Article  PubMed  Google Scholar 

  31. Poon RT, Fan ST, Lo CM et al (1999) Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg 229:216–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shimada K, Sano T, Sakamoto Y et al (2005) A long-term follow-up and management study of hepatocellular carcinoma patients surviving for 10 years or longer after curative hepatectomy. Cancer (Phila) 104:1939–1947

    Article  Google Scholar 

  33. Poon RT, Fan ST, Ng IO et al (2000) Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer (Phila) 89:500–507

    Article  CAS  Google Scholar 

  34. Shah SA, Cleary SP, Wei AC et al (2007) Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery (St. Louis) 141:330–339

    Article  Google Scholar 

  35. Tsai TJ, Chau GY, Lui WY et al (2000) Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma. Surgery (St. Louis) 127:603–608

    Article  CAS  Google Scholar 

  36. Cha C, Fong Y, Jarnagin WR et al (2003) Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg 197:753–758

    Article  PubMed  Google Scholar 

  37. Kondo K, Chijiiwa K, Makino I et al (2005) Risk factors for early death after liver resection in patients with solitary hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 12:399–404

    Article  PubMed  Google Scholar 

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Correspondence to Satoru Imura.

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Imura, S., Teraoku, H., Yoshikawa, M. et al. Potential predictive factors for microvascular invasion in hepatocellular carcinoma classified within the Milan criteria. Int J Clin Oncol 23, 98–103 (2018). https://doi.org/10.1007/s10147-017-1189-8

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  • DOI: https://doi.org/10.1007/s10147-017-1189-8

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